PURPOSE: The role of consolidation radiotherapy in patients with primary mediastinal B-cell lymphoma (PMBCL) is controversial. METHODS: The IELSG37 trial, a randomized noninferiority study, aimed to assess whether irradiation can be omitted in patients with PMBCL with complete metabolic response (CMR) after induction immunochemotherapy. The primary end point was progression-free survival (PFS) at 30 months after random assignment. Patients with CMR were randomly assigned to observation or consolidation radiotherapy (30 Gy). With a noninferiority margin of 10% (assuming a 30-month PFS of 85% in both arms), a sample size of 540 patients was planned with 376 expected to be randomly assigned. RESULTS: The observed events were considerably lower than expected; therefore, primary end point analysis was conducted when ≥95% of patients were followed for ≥30 months. Of the 545 patients enrolled, 268 were in CMR after induction and were randomly assigned to observation (n = 132) or radiotherapy (n = 136). The 30-month PFS was 96.2% in the observation arm and 98.5% in the radiotherapy arm, with a stratified hazard ratio of 1.47 (95% CI, 0.34 to 6.28) and absolute risk difference of 0.68% (95% CI, -0.97 to 7.46). The 5-year overall survival (OS) was 99% in both arms. Nonrandomized patients were managed according to local policies. Radiotherapy was the only treatment in 86% of those with Deauville score (DS) 4 and in 57% of those with DS 5. The 5-year PFS and OS of patients with DS 4 (95.8% and 97.5%, respectively) were not significantly different from those of randomly assigned patients. Patients with DS5 had significantly poorer 5-year PFS and OS (60.3% and 74.6%, respectively). CONCLUSION: This study, the largest randomized trial of radiotherapy in PMBCL, demonstrated favorable outcomes in patients achieving CMR with no survival impairment for those omitting irradiation.

• MeSH
• B-buněčný lymfom * radioterapie   mortalita   patologie   MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádory mediastina * radioterapie   mortalita   patologie   MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnocení ekvivalence MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Initial results from the ongoing GALLIUM trial have shown that patients with follicular lymphoma have a longer progression-free survival after first-line immunochemotherapy with obinutuzumab than with rituximab. The aim of this secondary analysis was to evaluate the prognostic value of PET-CT responses after first-line immunochemotherapy in the GALLIUM study. METHODS: GALLIUM is an open-label, parallel-group randomised, phase 3 trial, which recruited previously untreated patients with CD20-positive follicular lymphoma (grades 1-3a; disease stage III/IV, or stage II with largest tumour diameter ≥7 cm) who were aged 18 years or older and met the criteria for needing treatment. Eligible patients were randomly assigned in a 1:1 ratio to receive intravenous administration of obinutuzumab (1000 mg on days 1, 8, and 15 of cycle 1, then day 1 of subsequent cycles) or rituximab (375 mg/m2 on day 1 of each cycle), in six 21-day cycles with cyclophosphamide, doxorubicin, vincristine, and prednisone (known as CHOP; oral administration) followed by two 21-day cycles of antibody alone, or eight 21-day cycles cyclophosphamide, vincristine, and prednisone (known as CVP; oral administration), or six 28-day cycles with bendamustine, followed by maintenance antibody every 2 months for up to 2 years. The primary endpoint of the trial, investigator-assessed progression-free survival, has been reported previously. This secondary analysis reports PET and CT-based responses at end-of-induction therapy and explains their relation with progression-free and overall survival outcomes in patients with available scans. As per protocol, during the trial, PET scans (mandatory in the first 170 patients enrolled at sites with available PET facilities, and optional thereafter), acquired at baseline and end of induction (PET population), were assessed prospectively by investigators and an independent review committee (IRC) applying International Harmonisation Project (IHP) 2007 response criteria, and retrospectively by the IRC only applying current Lugano 2014 response criteria. IRC members (but not study investigators) were masked to treatment and clinical outcome when assessing response. The landmark analyses excluded patients who died or progressed (contrast enhanced CT-based assessment of progressive disease, or started next anti-lymphoma treatment) before or at end of induction. GALLIUM is registered at ClinicalTrials.gov, number NCT01332968. FINDINGS: 1202 patients were enrolled in GALLIUM between July 6, 2011, and Feb 4, 2014, of whom 595 were included in the PET population; 533 (IHP 2007; prospective analysis), and 508 (Lugano 2014; retrospective analysis) were analysed for progression-free survival (landmark analysis). At end of induction, 390 of 595 patients (65·5% [95% CI 61·6-69·4]) achieved PET complete response according to IHP 2007 criteria, and 450 (75·6% [95% CI 72·0-79·0]) obtained PET complete metabolic response according to Lugano 2014 criteria. With a median of 43·3 months of observation (IQR 36·2-51·8), 2·5-year progression-free survival from end of induction was 87·8% (95% CI 83·9-90·8) in PET complete responders and 72·0% (63·1-79·0) in non-complete responders according to IRC-assessed IHP 2007 criteria (hazard ratio [HR] 0·4, 95% CI 0·3-0·6, p<0·0001). According to Lugano 2014 criteria, 2·5-year progression-free survival in complete metabolic responders was 87·4% (95% CI 83·7-90·2) and in non-complete metabolic responders was 54·9% (40·5-67·3; HR 0·2, 95% CI 0·1-0·3, p<0·0001). INTERPRETATION: Our results suggest that PET is a better imaging modality than contrast-enhanced CT for response assessment after first-line immunochemotherapy in patients with follicular lymphoma. PET assessment according to Lugano 2014 response criteria provides a platform for investigation of response-adapted therapeutic approaches. Additional supportive data are welcomed. FUNDING: F Hoffmann-La Roche.

• MeSH
• časové faktory MeSH
• doba přežití bez progrese choroby MeSH
• folikulární lymfom diagnostické zobrazování   imunologie   mortalita   terapie   MeSH
• humanizované monoklonální protilátky aplikace a dávkování   škodlivé účinky   MeSH
• imunoterapie škodlivé účinky   metody   MeSH
• klinické zkoušky, fáze III jako téma MeSH
• lidé středního věku MeSH
• lidé MeSH
• počítačová rentgenová tomografie MeSH
• pozitronová emisní tomografie * MeSH
• prediktivní hodnota testů MeSH
• prospektivní studie MeSH
• protinádorové látky imunologicky aktivní aplikace a dávkování   škodlivé účinky   MeSH
• protokoly antitumorózní kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• randomizované kontrolované studie jako téma MeSH
• retrospektivní studie MeSH
• rituximab aplikace a dávkování   škodlivé účinky   MeSH
• senioři MeSH
• staging nádorů MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• tomografie emisní počítačová využití   metody   MeSH
• Publikační typ
• atlasy MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• chemie, klinická chemie
• radiologie, nukleární medicína a zobrazovací metody